USA – BioMarin Pharmaceutical plans to submit clinical trial results to the Food and Drug Administration later this year, claiming that its gene therapy for hemophilia can prevent bleeding for years after treatment.
The findings of BioMarin’s study, which were revealed ahead of the J.P. Morgan Healthcare Conference, are intended to meet the requirements laid out by the agency when it rejected the company’s previous approval application a year and a half ago.
They show that the gene therapy restored blood clotting protein levels to a range consistent with mild hemophilia, and that while those levels waned over time, trial participants experienced very few, if any, bleeds over the two years most were studied.
A small group of volunteers in the Phase 3 trial, the largest of its kind for a hemophilia gene therapy, were followed for three years and had similar outcomes.
“I believe that these results will answer, quantitatively, quite a lot of the questions that agencies have had,” said Hank Fuchs, BioMarin’s head of research and development, on a conference call.
European regulators have already begun evaluating BioMarin’s application and are expected to make a decision in the first half of this year.
In the United States, BioMarin intends to quickly review the results with the FDA and, if the agency agrees, resubmit the therapy in the second quarter.
BioMarin’s gene therapy, Roctavian, is the result of years of research by the California biotech, and it builds on the work of other scientists who have been working for more than a decade to develop a treatment for hemophilia’s genetic cause.
It is intended to deliver into the body a functional copy of the gene that has been mutated in people with hemophilia type “A,” who have little or no clotting protein to stop bleeding.
People with severe hemophilia A, which affects roughly half of all patients, must receive regular preventive infusions of “replacement” clotting protein, also known as Factor VIII.
Effective hemostatic agent
Roctavian, which is intended for these people, would theoretically allow them to stop, relieving them of chronic treatment while more effectively preventing bleeding.
Results from a previous, much smaller trial showed such promise that by mid-2020, BioMarin was on the verge of replicating those findings in the first group of volunteers enrolled in its Phase 3 study.
However, the FDA unexpectedly requested more information to prove that the benefit could last two years, according to the company.
BioMarin released one-year results from all trial participants in January, and on Sunday, it released data from its two-year analysis.
Treatment reduced the number of bleeds per year by 85 percent, from nearly five on average among the 112 volunteers who were studied for at least six months prior to infusion to less than one at year two.
The average annual bleeding rate among 17 participants who were given Roctavian three years prior to the study remained below one as well.
“Our clinical outcome here is unassailably great,” said Fuchs in a separate interview. “It almost makes the application, honestly, bulletproof.”
However, levels of Factor VIII activity, which had risen sharply to an average of 43 international units per deciliter of blood after one year, fell to 23 International Units/dL (IU/dL) by year two and 17 IU/dL by year three for those 17 participants.
BioMarin reported these results using a chromogenic assay, which it claims is more conservative than another method.
Severe hemophilia is defined as having less than one IU/dL of Factor VIII in the blood, whereas mild hemophilia is defined as having between 5 IU/dL and 40 IU/dL.
However, extrapolating efficacy puts BioMarin on shaky ground because it is the first company to make this far with a gene therapy for hemophilia A.
According to Jean-Jacques Bienaime, CEO of BioMarin, the data for Roctavian so far indicate that treatment should result in at least five years of bleeding control, and possibly eight or longer.
The FDA’s reaction to BioMarin’s data is unknown, though Wall Street analysts predicted the latest results would be sufficient to warrant approval.
It is also unclear how Roctavian will be perceived by hemophilia patients and insurers if it is approved.
BioMarin has previously suggested a price range of US$2 million to US$3 million, but that may be considered too high if Roctavian’s benefit isn’t lifelong.